Benzyl Bromide → HCID 57631694, compound

HRID 63760Notes

Reaction equation

HRID 63760 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]2[C:14]([CH3:16])([CH3:15])[CH2:13][CH:12]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:11][C:10]=12)=[O:5])C.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[H-].[Na+].[OH-].[K+]>C(O)C.CCOC(C)=O.CN(C=O)C>[CH2:23]([N:11]1[CH:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][C:14]([CH3:16])([CH3:15])[N:9]2[N:8]=[CH:7][C:6]([C:4]([OH:3])=[O:5])=[C:10]12)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 136059335HCID 136059335, compound

Product 1

HCID 57631694HCID 57631694, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a 100 mL round bottom flask equipped with a magnetic stir bar was added 1.80 g (6.01 mmol) of 7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester, 30 mL of DMF and 0.786 mL (6.61 mmol) of benzyl bromide, followed by 0.265 g (6.6 mmol) of sodium hydride (60% dispersion in mineral oil) which was added in several portions. After 2 h, the reaction was quenched with water and the product was extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to give the crude N-benzylated ester as a golden colored oil. The crude ester was dissolved in 15 mL of ethanol and 2.5 mL of 6N potassium hydroxide was added. The solution was then heated to 70° C. for 18 h at which time no starting material could be detected by HPLC analysis. The crude reaction mixture was concentrated in vacuo and diluted with water. The aqueous solution was acidified with 6N HCl and the resulting cream-colored precipitate was collected by filtration. The crude acid thus isolated was dissolved in AcOEt, dried over sodium sulfate, filtered and concentrated to a cream colored powder. The resulting acid was washed with several portions of hexanes and dried in vacuo to give 1.95 g (90%) of the title compound as an off white powder. 1H NMR (DMSO-d6) δ 1.10 (s, 3H), 1.40 (s, 3H), 1.98-2.16 (m, 2H), 3.71 (d, J=15.4 Hz, 1H), 4.36 (dd, J=4.5, 11.5 Hz, 1H), 5.81 (d, J=15.6 Hz), 6.97 (dd, J=1.4, 7.2 Hz, 2H), 7.26-7.45 (m, 7H), 7.67 (s, 1H), 11.81 (s, 1H). MS Calcd.: 361. Found: 344 (M−OH).

Workup

  1. customTo a 100 mL round bottom flask equipped with a magnetic stir bar
  2. additionwas added in several portions
  3. customthe reaction was quenched with water
  4. extractionthe product was extracted with AcOEt
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude N-benzylated ester as a golden colored oil
  10. customThe crude reaction mixture
  11. concentrationwas concentrated in vacuo
  12. additiondiluted with water
  13. filtrationthe resulting cream-colored precipitate was collected by filtration
  14. customThe crude acid thus isolated
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated to a cream
  18. washThe resulting acid was washed with several portions of hexanes
  19. customdried in vacuo

Sources & evidence

ORD record
ord-cd71e248d7884803b0edad37493f4ce7
Source dataset
uspto-grants-2016_09
Patent number
US09447100B2

Reaction notes

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